Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis. Issue 2 (30th September 2014)

• Record Type: Journal Article
• Authors: Terada, Yuka; Fujimura, Mayuko; Nishimura, Sachiyo; Tsubota, Maho; Sekiguchi, Fumiko; Kawabata, Atsufumi
• Is Part Of: Journal of neuroscience research. Volume 93:Issue 2(2015)
• Page Start: 361
• Page End: 369
• Publication Date: 2014-09-30
• Subjects: Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.23490
• Languages: English
• ISSNs: 0360-4012

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Hydrogen sulfide (H<sub>2</sub>S), formed by multiple enzymes, including cystathionine‐γ‐lyase (CSE), targets Ca<sub>v</sub>3.2 T‐type Ca<sup>2+</sup> channels (T channels) and transient receptor potential ankyrin‐1 (TRPA1), facilitating somatic pain. Pancreatitis‐related pain also appears to involve activation of T channels by H<sub>2</sub>S formed by the upregulated CSE. Therefore, this study investigates the roles of the Ca<sub>v</sub>3.2 isoform and/or TRPA1 in pancreatic nociception in the absence and presence of pancreatitis. In anesthetized mice, AP18, a TRPA1 inhibitor, abolished the Fos expression in the spinal dorsal horn caused by injection of a TRPA1 agonist into the pancreatic duct. As did mibefradil, a T‐channel inhibitor, in our previous report, AP18 prevented the Fos expression following ductal NaHS, an H<sub>2</sub>S donor. In the mice with cerulein‐induced acute pancreatitis, the referred hyperalgesia was suppressed by NNC 55‐0396 (NNC), a selective T‐channel inhibitor; zinc chloride; or ascorbic acid, known to inhibit Ca<sub>v</sub>3.2 selectively among three T‐channel isoforms; and knockdown of Ca<sub>v</sub>3.2. In contrast, AP18 and knockdown of TRPA1 had no significant effect on the cerulein‐induced referred hyperalgesia, although they significantly potentiated the antihyperalgesic effect of NNC at a subeffective dose. TRPA1 but not Ca<sub>v</sub>3.2 in the dorsal root ganglia was downregulated at a protein level in mice with cerulein‐induced pancreatitis. The data indicate that TRPA1 and Ca<sub>v</sub>3.2 mediate the exogenous H<sub>2</sub>S‐induced pancreatic nociception in naïve mice and suggest that, in the mice with pancreatitis, Ca<sub>v</sub>3.2 targeted by H<sub>2</sub>S primarily participates in the pancreatic pain, whereas TRPA1 is downregulated and plays a secondary role in pancreatic nociceptive signaling. © 2014 Wiley Periodicals, Inc.</p> </abstract>